A pharmacovigilance study of adverse events associated with polycythemia vera treatments using the FDA Adverse Event Reporting System (FAERS) database.
Academic Article
Overview
abstract
Cytoreductive therapies remain vital to the management of polycythemia vera (PV). Real-world data are needed to complement clinical trial safety information. We evaluated the safety profiles of four commonly used PV therapies—ropeginterferon alfa-2b (ropeg, on-label), peginterferon alfa-2a (peg-IFN, off-label), ruxolitinib (on-label), and hydroxyurea (HU, off-label)—using the FDA Adverse Event Reporting System (FAERS) database. Among 97,812 adverse event (AE) reports for patients receiving cytoreduction from January 1, 2022, through December 31, 2024, 11,754 were analyzed. HU and peg-IFN showed elevated reporting odds ratios (RORs) for serious adverse events (SAEs), which increased over time for HU (8.55 in 2022, 13.46 in 2023, 16.04 in 2024) and peaked for peg-IFN in 2023 (22.25). Ruxolitinib had ROR > 1 only in 2023 (1.47), while ropeg had no RORs > 1 for SAEs. For fatal AEs, ruxolitinib demonstrated RORs > 1 across multiple years (15.74 in 2022, 5.07 in 2023, 4.47 in 2024), whereas HU, peg-IFN, and ropeg did not. HU and ruxolitinib were associated with higher reporting of blood and lymphatic disorders than ropeg and peg-IFN, while peg-IFN had the highest proportion of cardiac disorder AEs (4.38%). HU (8.24%) and ruxolitinib (2.79%) showed elevated neoplasm-related AE proportions compared with peg-IFN (1.46%) and ropeg (0.65%). Ropeg showed the highest RORs for non-serious AEs. Contrary to clinical trial data, psychiatric disorders were most reported with ropeg (5.79%). An exploratory age-stratified analysis was also performed, though interpretation was limited by missing age data. These real-world findings provide valuable insights into the long-term risk-benefit profiles of cytoreductive therapies in PV and can guide personalized treatment strategies. Further studies are warranted to confirm these observations.
